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- Meira de Faria, Felipe, et al.
(författare)
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Colonic paracellular permeability and circulating zonulin-related proteins
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Objective Irritable bowel syndrome (IBS) is a gut-brain disorder associated with increased gut permeability. Zonulin has been suggested to regulate the gut barrier and claimed to be pre-haptoglobin 2 (pre-HP2) and circulating zonulin is often used as a proxy for gastrointestinal permeability. This study investigated the correlation between colonic paracellular permeability and levels of circulating zonulin and pre-HP2. Materials and Methods Colonic biopsies from 32 patients with IBS and 15 healthy controls (HC) were used to measure permeability in Ussing chambers and levels of zonulin (Cusabio ELISA). Zonulin was also measured in blood samples from 40 HC, 78 patients with IBS and 20 patients with celiac disease (CeD), before and after a gluten-free diet. In addition, we verified HP genotype and circulating pre-HP2 using a monoclonal pre-HP2 antibody (Bio-Rad) by ELISA. Results Increased colonic paracellular permeability correlated positively with zonulin levels in IBS biopsies, but negatively with plasma zonulin. We found no agreement between circulating zonulin and pre-HP2. Genotyping revealed non-specificity of the zonulin kit, as all pre-HP2 non-producers presented detectable levels. Patients with CeD displayed higher pre-HP2 and zonulin levels compared to HC. A gluten-free diet in patients with CeD led to lower serum zonulin and pre-HP2 concentrations. Conclusions Our study suggests that neither circulating zonulin nor pre-HP2 mirror colonic permeability. Our data corroborate previous reports showing the inability of the Cusabio zonulin kit to target zonulin and highlights that the results of studies using this kit must be re-examined with caution.
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| 2. |
- Norlin, Anna-Karin, 1977-, et al.
(författare)
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Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity
- 2021
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Ingår i: Brain, behavior, and immunity. - Amsterdam, Netherlands : Elsevier. - 0889-1591 .- 1090-2139. ; 92, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a symptom-based disorder of gut-brain interactions generating abdominal pain. It is also associated with a vulnerability to develop extraintestinal symptoms, with fatigue often reported as one of the most disturbing. Fatigue is related to brain function and inflammation in several disorders, however, the mechanisms of such relations in IBS remain elusive. This study aimed to elucidate fatigue and its association with a resting state network of mesocorticolimbic regions of known importance in fatigue, and to explore the possible role of circulating TNF-α levels in IBS and healthy controls (HC). Resting state functional magnetic resonance imaging (fMRI) was conducted in 88 IBS patients and 47 HC of similar age and gender to investigate functional connectivity between mesocorticolimbic regions. Further, fatigue impact on daily life and plasma levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), of known relevance to immune activation in IBS, were also measured. The selected mesocorticolimbic regions indeed formed a functionally connected network in all participants. The nucleus accumbens (NAc), in particular, exhibited functional connectivity to all other regions of interest. In IBS, fatigue impact on daily life was negatively correlated with the connectivity between NAc and dorsolateral prefrontal cortex bilaterally (left p = 0.019; right p = 0.038, corrected for multiple comparisons), while in HC, fatigue impact on daily life was positively correlated to the connectivity between the right NAc and anterior middle insula in both hemispheres (left p = 0.009; right p = 0.011). We found significantly higher levels of TNF-α in IBS patients compared to HC (p = 0.001) as well as a positive correlation between TNF-α and fatigue impact on daily life in IBS patients (rho = 0.25, p = 0.02) but not in HC (rho = −0.13, p = 0.37). There was no association between functional connectivity in the mesocorticolimbic network and plasma levels of TNF-α in either group In summary, this novel multimodal study provides the first evidence that the vulnerability to fatigue in IBS is associated with connectivity within a mesocorticolimbic network as well as immune activation. These findings warrant further investigation, both peripherally and potentially with measurements of central immune activation as well.
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| 3. |
- Simon, Rozalyn, 1979-, et al.
(författare)
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Magnetotactic bacteria from the human gut microbiome associated with orientation and navigation regions of the brain
- 2021
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Ingår i: Journal of Oceanology and Limnology. - : Springer Nature. - 2096-5508 .- 2523-3521. ; 39:6, s. 2044-2052
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Tidskriftsartikel (refereegranskat)abstract
- Magnetotactic bacteria (MTB), ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals. MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields. Similar magnetite deposits have been found throughout the tissues of the human brain, including brain regions associated with orientation such as the cerebellum and hippocampus, the origins of which remain unknown. Speculation over the role and source of MTB in humans, as well as any association with the brain, remain unanswered. We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions. We identified seven MTB in the human gut microbiome: Magnetococcus marinus, Magnetospira sp. QH-2, Magnetospirillum magneticum, Magnetospirillum sp. ME-1, Magnetospirillum sp. XM-1, Magnetospirillum gryphiswaldense, and Desulfovibrio magneticus. Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus (adjusted for total intracranial volume, uncorrected P<0.05). These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation. These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans. Further studies will be necessary to validate and elucidate the relationship between these bacteria, magnetite concentrations, and brain function.
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| 4. |
- Simon, Rozalyn, et al.
(författare)
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Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females
- 2021
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood-brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r=- 0.44, p=0.002) and depression (r=- 0.50, p=0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t((33))=3.1, p(FDR)=0.02) and right lateral orbitofrontal cortex (OFC; t((33))=2.9, p(FDR)=0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r=0.28, p=0.007) and left lateral OFC (r=0.29, p=0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.
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